Does thioredoxin-1 prevent mitochondria- and endoplasmic reticulum-mediated neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine?
| Autor: | Jie Bai, Hajime Nakamura, Toru Tanaka, Satoshi Ogawa, Takashi Momoi, Sadayuki Ban, Itaro Hattori, Yasuko Kitao, Junji Yodoi, Masaki Tanito, Shugo Ueda, Yong-Won Kwon |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Programmed cell death 1-Methyl-4-phenylpyridinium Physiology Clinical Biochemistry Neurotoxins Mice Transgenic Mitochondrion Endoplasmic Reticulum Biochemistry PC12 Cells chemistry.chemical_compound Mice Thioredoxins medicine Animals Humans Cytotoxicity Molecular Biology General Environmental Science chemistry.chemical_classification Reactive oxygen species Cell Death MPTP Endoplasmic reticulum Neurotoxicity Cell Biology medicine.disease Molecular biology Cell biology Mitochondria Rats Mice Inbred C57BL chemistry Apoptosis 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine General Earth and Planetary Sciences HeLa Cells Signal Transduction |
| Zdroj: | Antioxidantsredox signaling. 9(5) |
| ISSN: | 1523-0864 |
| Popis: | We show that 1-methyl-4-phenylpyridinium ion (MPP(+)), an active metabolite of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), induces cytotoxicity via endoplasmic reticulum (ER)- and mitochondria-mediated pathways, and thioredoxin-1 (TRX-1), a redox-active protein, prevents MPTP-induced neurotoxicity. TRX-1 overexpression suppressed reactive oxygen species and the ATP decline caused by MPP(+) in HepG2 cells. MPP(+) activated caspase-12 in PC12 cells and induced cytotoxicity in HeLa-rho(0) cells lacking mitochondrial DNA, as well as in the parental HeLa-S3 cells. TRX-1-transgenic mice demonstrated significant resistance to caspase-12 activation and the apoptotic decrease of dopaminergic neurons after MPTP administration, compared with wild-type C57BL/6 mice. |
| Databáze: | OpenAIRE |
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